Enteric Fever Cases in the Two Largest Pediatric Hospitals of Bangladesh: 2013–2014 Shampa Saha,1 Mohammad J
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The Journal of Infectious Diseases SUPPLEMENT ARTICLE Enteric Fever Cases in the Two Largest Pediatric Hospitals of Bangladesh: 2013–2014 Shampa Saha,1 Mohammad J. Uddin,1 Maksuda Islam,1 Rajib C. Das,1,a Denise Garrett,2 and Samir Kumar Saha1,3, 1Child Health Research Foundation, Department of Microbiology, Dhaka Shishu (Children) Hospital, Bangladesh; 2Sabin Vaccine Institute, Washington, DC; 3Bangladesh Institute of Child Health, Dhaka Shishu (Children) Hospital, Bangladesh Background. Enteric fever predominantly affects children in low- and middle-income countries. This study examines the bur- den of enteric fever at the 2 pediatric hospitals in Dhaka, Bangladesh and assesses their capacity for inclusion in a prospective cohort study to support enteric fever prevention and control. Methods. A descriptive study of enteric fever was conducted among children admitted in 2013–2014 to inpatient departments of Dhaka Shishu and Shishu Shashthya Foundation Hospitals, sentinel hospitals of the World Health Organization-supported Invasive Bacterial Vaccine Preventable Disease surveillance platform. Results. Of 15 917 children with blood specimens received by laboratories, 2.8% (443 of 15 917) were culture positive for signif- icant bacterial growth. Sixty-three percent (279 of 443) of these isolates were confirmed as the cases of enteric fever (241Salmonella Typhi and 38 Salmonella Paratyphi A). In addition, 1591 children had suspected enteric fever. Overall, 3.6% (1870 of 51 923) were laboratory confirmed or suspected enteric fever cases (55% male, median age 2 years, 86% from Dhaka district, median hospital stay 5 days). Conclusions. The burden of enteric fever among inpatients at 2 pediatric hospitals in Dhaka, Bangladesh is substantial. Therefore, inclusion of these hospitals in a prospective cohort study will be useful for the generation of credible disease burden estimates of enteric fever in Bangladesh. Keywords. Bangladesh; enteric fever; hospital; Salmonella; surveillance. Enteric fever is an acute, systemic infectious disease caused The establishment of a comprehensive surveillance system is by the bacteria Salmonella enterica serovars Typhi and important for generating credible data on enteric fever disease Paratyphi A, B, or C, which often manifests with high-grade burden in endemic regions [10]. In Bangladesh, there was no fever, coated tongue, nausea or vomiting, diarrhea, abdom- comprehensive surveillance that systematically collected infor- inal pain, and cough [1]. It predominantly affects children mation on enteric fever for measuring burden of the disease. and young adults because they either lack natural immunity To date, the burden of enteric fever in Bangladesh has been or experience high levels of exposure to fecal pathogens [2, 3]. estimated on the basis of studies conducted in an urban slum STANDARD Each year, approximately 16 million cases of illness and over [11, 12]. Some hospital-based studies that estimated burden 153 000 deaths are attributed to enteric fever, although esti- of enteric fever included hospitalized cases only [13, 14]. The mates vary and are uncertain due to the limited number of pop- lack of credible estimates for enteric fever incidence, compli- ulation-based incidence studies [4]. In addition, enteric fever cations, and mortality rates has hampered the establishment continues to be an important global health problem especially of evidence-based policy decisions to prevent and control this in low- and middle-income countries of South Asia, including disease [15]. Bangladesh [2, 4–8]. These low-resource countries experience a To fill these knowledge gaps, the Surveillance for Enteric high burden of enteric fever because they have limited access to fever in Asia Project (SEAP), a phased, comprehensive, mul- safe drinking water and to adequate sanitation and hygiene [2, 9]. ticountry, and multisite study, was initiated. The SEAP’s over- all objectives are to characterize the burden of enteric fever in selected Asian settings, including clinical manifestations, sever- aPresent Affiliation: Evaluation Officer, Bangladesh Handloom Board (Ministry of Textiles and ity of illness, long-term sequelae of illness, antimicrobial resis- Jute), 7–9 Kawran Bazar. Correspondence: S. K. Saha, PhD, Executive Director, Child Health Research Foundation, and tance patterns of Salmonella Typhi and Paratyphi, and cost of Professor and Head, Department of Microbiology, Bangladesh, Institute of Child Health, Dhaka illness. The SEAP study will generate baseline data to inform Shishu Hospital, Sher-E-Bangla Nagar, Dhaka-1207, Bangladesh ([email protected]). appropriate interventions for enteric fever prevention and con- The Journal of Infectious Diseases® 2018;218(S4):S195–200 © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society trol and facilitate the assessment of the impact of interventions of America. This is an Open Access article distributed under the terms of the Creative Commons while also characterizing risk factors for the development of Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. severe illness among enteric fever cases. Phase I of the SEAP DOI: 10.1093/infdis/jiy521 was aimed at collecting data on enteric fever cases in 4 countries Enteric Fever Among Children of Urban Dhaka • JID 2018:218 (Suppl 4) • S195 (Bangladesh, India, Pakistan, and Nepal) to assess health facil- Detection of Salmonella Typhi and Salmonella Paratyphi in Blood ities with the potential to participate in and guide the design of Samples Phase II of the project, a prospective surveillance study to be All blood cultures were performed using standard methods conducted at selected hospitals and laboratory networks in 3 [16]. In briefly, 2–3 mL blood was obtained under aseptic con- endemic countries, namely, Bangladesh, Nepal, and Pakistan. dition and inoculated into Trypticase soy broth supplemented In this study, we provide descriptive data from the SEAP Phase with sodium polyethanol sulphonate (0.25%) and isovitalex I to assess the burden of enteric fever at 2 pediatric hospitals in (1%). After incubation, blood culture bottles were subcultured Dhaka, Bangladesh as well as evaluate their capacity to partici- on second, third, and fifth days of incubation. Standard bio- pate in a prospective cohort study. chemical tests and agglutination with Salmonella species and serovar specific antisera (Ramel; Thermo Fisher Scientific) METHODS were used to confirmSalmonella Typhi/Paratyphi isolates. To Study Design, Sites, and Procedures ensure the quality of the laboratories, we have both internal and Data for the SEAP Phase I were gathered retrospectively from external quality control (QC) systems in place. Internal QC of an ongoing surveillance project during 2013–2014 among inpa- the laboratories is performed at quarterly basis. External QC is tient departments (IPDs) of 2 hospitals in Dhaka, Bangladesh: performed once a year by United Kingdom National External (1) Dhaka Shishu (Children) Hospital (DSH) and (2) Shishu Quality Assessment Scheme as part of QC of IB-VPD surveil- Sashthya (Child Health) Foundation Hospital (SSFH). The DSH lance. In addition, we send specimens to the Center for Disease is the largest pediatric hospital in Bangladesh that provides pri- Control and Prevention to determine whether the results were mary, secondary, and tertiary care to patients less than 18 years concordant. Blood culture volume is regularly monitored in the of age; 37% of the 640 beds in DSH are reserved for patients laboratories. who are unable to pay. With 200 beds, SSFH is the second larg- Data Analysis est pediatric (patients <18 years) hospital in the country and All analyses were performed using the STATA 13.1 (StataCorp provides primary care only; 5% of admitted patients are pro- LP, College Station, TX). Summary statistics included vided care free of charge. In both hospitals, blood specimens are median ± interquartile range (IQR) for continuous variables collected at the treating physician’s discretion and processed in and frequencies with percentages for categorical variables. the in-house microbiology laboratories. Comparative statistics included independent samples t test, These 2 hospitals are sentinel sites of the World Health Wilcoxon’s rank-sum test, χ2 test, and Fisher’s exact test, as Organization (WHO)-coordinated Invasive Bacterial Vaccine appropriate. Two-sided statistical tests were conducted at an Preventable Disease (IB-VPD) surveillance. In our ongoing alpha level of 0.05. WHO-supported IB-VPD surveillance at DSH and SSFH, we collect detailed demographic, clinical, and laboratory informa- Ethical Consideration tion electronically on hospitalized suspected and laboratory-con- Approval for analysis of secondary data for SEAP Phase I was firmed pneumonia, sepsis, meningitis, and enteric fever cases who obtained from the Ethical Review Committee of Bangladesh are younger than 5 years. The inclusion criteria for enteric fever is Institute of Child Health, Dhaka, with a waiver of informed ≥38.9°C for ≥3 days [6]. Minimal demographic and clinical infor- consent. mation (for example, age, sex, diagnoses on admission and dis- charge, hospital duration, etc) of the hospitalized children who are RESULTS not enrolled in IB-VPD surveillance are recorded in the hospital Enteric Fever Cases Identified at Each Site database. For the present